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Side Effects
Interactions

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

ERIVEDGE capsule was administered as monotherapy at doses ≥ 150 mg orally daily in four open-label, uncontrolled, dose-ranging or fixed single dose clinical trials enrolling a total of 138 patients with advanced basal cell carcinoma (BCC). The median age of these patients was 61 years (range 21 to 101), 100% were White (including Hispanics), and 64% were male. The median duration of treatment was approximately 10 months (305 days; range 0.7 to 36 months); 111 patients received ERIVEDGE for 6 months or longer.

The most common adverse reactions ( ≥ 10%) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia (Table 1).

Table 1: Adverse Reactions Occurring in ≥ 10% of Advanced BCC Patients

MedDRA Preferred Term2 All aBCC1 Patients (N = 138)
All Grades3 (%) Grade 3 (%) Grade 4 (%)
Gastrointestinal disorders
  Nausea 42 (30.4%) 1 (0.7%) -
  Diarrhea 40 (29.0%) 1 (0.7%) -
  Constipation 29 (21.0%) - -
  Vomiting 19 (13.8%) - -
General disorders and administration site conditions
  Fatigue 55 (39.9%) 7 (5.1%) 1 (0.7%)
Investigations
  Weight loss 62 (44.9%) 10 (7.2%) -
Metabolism and nutrition disorders
  Decreased appetite 35 (25.4%) 3 (2.2%) -
Musculoskeletal and connective tissue disorders
  Muscle spasms 99 (71.7%) 5 (3.6%) -
  Arthralgias 22 (15.9%) 1 (0.7%)
Nervous system disorders
  Dysgeusia 76 (55.1%) - -
  Ageusia 15 (10.9%) - -
Skin and subcutaneous tissue disorders
  Alopecia 88 (63.8%) - -
1aBCC = Advanced Basal Cell Carcinoma.
2MedDRA = Medical Dictionary for Regulatory Activities.
3Grading according to NCI-CTCAE v3.0.

Amenorrhea

In clinical trials, a total of 3 of 10 pre-menopausal women developed amenorrhea while receiving ERIVEDGE [see Non-Clinical Toxicology].

Laboratory Abnormalities

Treatment-emergent Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia in 6 patients (4%), hypokalemia in 2 patients (1%), and azotemia in 3 patients (2%).

Read the Erivedge (vismodegib) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Effects of Other Drugs on Vismodegib

Drugs that Inhibit or Induce Drug Metabolizing Enzymes

Vismodegib elimination involves multiple pathways. Vismodegib is predominantly excreted as an unchanged drug. Several minor metabolites are produced by multiple CYP enzymes. Although vismodegib is a substrate of CYP2C9 and CYP3A4 in vitro, CYP inhibition is not predicted to alter vismodegib systemic exposure since similar steady-state plasma vismodegib concentrations were observed in patients in clinical trials concomitantly treated with CYP3A4 inducers (i.e., carbamazepine, modafinil, phenobarbital) and those concomitantly treated with CYP3A4 inhibitors (i.e., erythromycin, fluconazole).

Drugs that Inhibit Drug Transport Systems

In vitro studies indicate that vismodegib is a substrate of the efflux transporter P-glycoprotein (P-gp). When ERIVEDGE is coadministered with drugs that inhibit P-gp (e.g. clarithromycin, erythromycin, azithromycin), systemic exposure of vismodegib and incidence of adverse events of ERIVEDGE may be increased.

Drugs that Affect Gastric pH

Drugs that alter the pH of the upper GI tract (e.g. proton pump inhibitors, H2-receptor antagonists, and antacids) may alter the solubility of vismodegib and reduce its bioavailability. However, no formal clinical study has been conducted to evaluate the effect of gastric pH altering agents on the systemic exposure of vismodegib. Increasing the dose of ERIVEDGE when coadministered with such agents is not likely to compensate for the loss of exposure. When ERIVEDGE is coadministered with a proton pump inhibitor, H2-receptor antagonist or antacid, systemic exposure of vismodegib may be decreased and the effect on efficacy of ERIVEDGE is unknown.

Effects of Vismodegib on Other Drugs

Results of a drug-drug interaction study conducted in cancer patients demonstrated that the systemic exposure of rosiglitazone (a CYP2C8 substrate) or oral contraceptives (ethinyl estradiol and norethindrone) is not altered when either drug is co-administered with vismodegib.

In vitro studies indicate that vismodegib is an inhibitor of CYP2C8, CYP2C9, CYP2C19 and the transporter BCRP. Vismodegib does not induce CYP1A2, CYP2B6, or CYP3A4/5 in human hepatocytes.

Read the Erivedge Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 2/2/2012
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
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